Anti-monocyte chemoattractant protein-1 gene therapy prevents dimethylnitrosamine-induced hepatic fibrosis in rats

  • Authors:
    • Satoru Tsuruta
    • Makoto Nakamuta
    • Munechika Enjoji
    • Kazuhiro Kotoh
    • Kenichi Hiasa
    • Kensuke Egashira
    • Hajime Nawata
  • View Affiliations

  • Published online on: November 1, 2004     https://doi.org/10.3892/ijmm.14.5.837
  • Pages: 837-842
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Abstract

Monocyte chemoattractant protein-1 (MCP-1) has been implicated in the process of hepatic inflammation, recruiting monocytes and lymphocytes during liver injury. MCP-1 also activates directly hepatic stellate cells, which play a major role in hepatic fibrosis. However, it remains unclear whether blockage of MCP-1 signaling could prevent hepatic fibrosis in vivo. We evaluated a strategy for anti-MCP-1 gene therapy against hepatic fibrosis by transfecting an amino-terminal deletion mutant, lacking the amino-terminal codons 2 to 8 of the human MCP-1 gene and designated 7ND, into skeletal muscle in a rat experimental model of dimethylnitrosamine (DMN)-induced fibrosis. Anti-MCP-1 gene therapy decreased significantly the occurrence of DMN-induced hepatic fibrosis, evaluated by computed image analysis and by measurement of hydroxyproline contents of the liver, accompanied by a reduction in the expressions of α-smooth muscle actin. This treatment also caused a significant decrease in hepatic tissue levels of interleukin (IL)-12 (Th1 cytokine) and an increase in those of IL-10 (Th2 cytokine), indicating a change in the Th1/Th2 cytokine balance in the liver. In conclusion, blockade of MCP-1 after intramuscular transfer of the 7ND gene suppressed hepatic fibrosis, and this strategy may be a useful and feasible gene therapy against hepatic fibrosis.

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November 2004
Volume 14 Issue 5

Print ISSN: 1107-3756
Online ISSN:1791-244X

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Spandidos Publications style
Tsuruta S, Nakamuta M, Enjoji M, Kotoh K, Hiasa K, Egashira K and Nawata H: Anti-monocyte chemoattractant protein-1 gene therapy prevents dimethylnitrosamine-induced hepatic fibrosis in rats. Int J Mol Med 14: 837-842, 2004.
APA
Tsuruta, S., Nakamuta, M., Enjoji, M., Kotoh, K., Hiasa, K., Egashira, K., & Nawata, H. (2004). Anti-monocyte chemoattractant protein-1 gene therapy prevents dimethylnitrosamine-induced hepatic fibrosis in rats. International Journal of Molecular Medicine, 14, 837-842. https://doi.org/10.3892/ijmm.14.5.837
MLA
Tsuruta, S., Nakamuta, M., Enjoji, M., Kotoh, K., Hiasa, K., Egashira, K., Nawata, H."Anti-monocyte chemoattractant protein-1 gene therapy prevents dimethylnitrosamine-induced hepatic fibrosis in rats". International Journal of Molecular Medicine 14.5 (2004): 837-842.
Chicago
Tsuruta, S., Nakamuta, M., Enjoji, M., Kotoh, K., Hiasa, K., Egashira, K., Nawata, H."Anti-monocyte chemoattractant protein-1 gene therapy prevents dimethylnitrosamine-induced hepatic fibrosis in rats". International Journal of Molecular Medicine 14, no. 5 (2004): 837-842. https://doi.org/10.3892/ijmm.14.5.837